HIV is known to productively infect a variety of different cell types in vitro and in vivo. The extent to which HIV infects and replicates in these cells has important implications concerning dissemination from portals of entry, cell function, and disease progression given the finite number of target cells. End products of viral replication including expression of unspliced HIV mRNA and plasma free virus has led to virologic determinants as a measure of disease state and therapeutic efficacy. A marked increase in the ratio of unspliced to spliced HIV mRNA as might occur during the shift from latent to productive infection precedes precipitous drops in CD4 count. Plasma viral load has been shown to correlate with disease progression and has been used to determine HIV kinetics in viva. These measurements, however, fail to provide information on the cell type of origin-a weakness considering the effects of HIV expression on cell function, the role of infected cells in transmission and dissemination, and the therapeutic potential of blocking cell type specific co-receptors.
Plasma viral burden analysis have allowed researchers to estimate kinetic parameters of HIV-1 life cycle in vivo. The life span of productively infected T-lymphocytes was estimated to be 2.2 days. The detection and quantification of productively infected lymphocytes, therefore, is technically difficult requiring very sensitive techniques. Further, the turnover of these cells may be too rapid to measure these cells on a continuous basis. In addition, the contribution of free virus to the infective pool by cell types not destroyed by viral replication has not been experimentally addressed and has only been included as an aside in most kinetic models.
The transmission of HIV characteristically involves the early appearance of NSI (non-syncitial inducing), macrophage tropic viral isolates despite the presence or absence of SI (syncitial inducing) and NSI variants in the donor. Effective anti-HIV immune responses have been suggested to temper the replication of SI variants after transmission. Following seroconversion, SI variants start to appear as a result of immune dysfunction. Some studies, however, suggest that NSI, macrophage tropic isolates persist throughout the disease course in spite of the abundance of SI variants.
Recent data lends support to the model that selective transmission may occur as the virus penetrates mucosal surfaces and encounters cells of monocyte/macrophage lineage. The virus can then be distributed throughout the lymphoid system and tissue compartments via these cells. Once in the lymphoid compartment, the virus encounters the overwhelming majority of the body's lymphocytes. The virus accumulates in and eventually destroys the T-cell reservoir leaving only macrophages in T-cell depleted lymph nodes. Although free virus determinations have helped define HIV-1 kinetics in vivo, resent elucidation of macrophage and T-cell tropic coreceptors demands further characterizations of the cells producing virus at various times during disease progression and during antiretroviral therapy.